Andrographolide engineered gold nanoparticle to overcome drug resistant visceral leishmaniasis.
08 Feb 2018-Artificial Cells Nanomedicine and Biotechnology (Artif Cells Nanomed Biotechnol)-Vol. 46, pp 751-762
TL;DR: This study aims to arrive at terpenoid andrographolide engineered gold nanoparticle (AGAunps) facile synthesis and its efficacy evaluations against wild and drug resistant VL strains for the first time.
Abstract: Visceral leishmaniasis (VL) is World Health Organization designated most serious leishmaniasis with an annual mortality rate of 50,000. Even after country specific eradication programs, the disease...
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TL;DR: GNP-based delivery of AmB can be a better, cheaper, and safer alternative than available AmB formulations, and improved antileishmanial efficacy and reduced cytotoxicity.
Abstract: Background Amphotericin B (AmB) as a liposomal formulation of AmBisome is the first line of treatment for the disease, visceral leishmaniasis, caused by the parasite Leishmania donovani. However, nephrotoxicity is very common due to poor water solubility and aggregation of AmB. This study aimed to develop a water-soluble covalent conjugate of gold nanoparticle (GNP) with AmB for improved antileishmanial efficacy and reduced cytotoxicity. Methods Citrate-reduced GNPs (~39 nm) were functionalized with lipoic acid (LA), and the product GNP-LA (GL ~46 nm) was covalently conjugated with AmB using carboxyl-to-amine coupling chemistry to produce GNP-LA-AmB (GL-AmB ~48 nm). The nanoparticles were characterized by dynamic light scattering, transmission electron microscopy (TEM), and spectroscopic (ultraviolet-visible and infrared) methods. Experiments on AmB uptake of macrophages, ergosterol depletion of drug-treated parasites, cytokine ELISA, fluorescence anisotropy, flow cytometry, and gene expression studies established efficacy of GL-AmB over standard AmB. Results Infrared spectroscopy confirmed the presence of a covalent amide bond in the conjugate. TEM images showed uniform size with smooth surfaces of GL-AmB nanoparticles. Efficiency of AmB conjugation was ~78%. Incubation in serum for 72 h showed <7% AmB release, indicating high stability of conjugate GL-AmB. GL-AmB with AmB equivalents showed ~5-fold enhanced antileishmanial activity compared with AmB against parasite-infected macrophages ex vivo. Macrophages treated with GL-AmB showed increased immunostimulatory Th1 (IL-12 and interferon-γ) response compared with standard AmB. In parallel, AmB uptake was ~5.5 and ~3.7-fold higher for GL-AmB-treated (P<0.001) macrophages within 1 and 2 h of treatment, respectively. The ergosterol content in GL-AmB-treated parasites was ~2-fold reduced compared with AmB-treated parasites. Moreover, GL-AmB was significantly less cytotoxic and hemolytic than AmB (P<0.01). Conclusion GNP-based delivery of AmB can be a better, cheaper, and safer alternative than available AmB formulations.
37 citations
Additional excerpts
...5-25) (1-108) (1-108) GNP (μg/mL) GL (μg/mL) AmB (μM) GL-AmB (μM) *** *** *** *** ***...
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Chinese Ministry of Education1, Shanghai University2, Nanjing University of Chinese Medicine3, Beijing University of Chinese Medicine4, Tianjin University of Traditional Chinese Medicine5, Chengdu University of Traditional Chinese Medicine6, Chinese Academy of Sciences7, China Pharmaceutical University8, Guangzhou University of Chinese Medicine9, Guizhou University10, Fujian University of Traditional Chinese Medicine11, Fudan University12, Yale University13, Peking University14, Zhejiang University15
TL;DR: In this article, the authors discuss the overlapping connectivity and relevance of the two fields, including nanoaggregates generated in herbal medicine decoctions, the application of nanotechnology in the delivery and treatment of natural active ingredients, and the influence of physiological regulatory capability of traditional herbal medicine on the in vivo fate of nanoparticles.
37 citations
TL;DR: This review reports on published studies related to microparticles (MPs) and nanoparticles (NPs) loaded with Andrographolide and improved bioavailability, target-tissue distribution, and efficacy of AG loaded in the described drug delivery systems have been reported.
34 citations
TL;DR: In this article, the main emphasis was given on the anticancer activity of AG, its proposed mechanisms of action, novel approaches used to improve its biopharmaceutical properties, and its development as an adjuvant therapy for cancer treatment in future.
26 citations
TL;DR: In this article, the role of physicochemical properties of a nanoscale delivery system is discussed and different ways of nano-formulation delivery ranging from liposome, niosomes, polymeric, metallic, solid-lipid NPs were updated along with the possible mechanisms of action against the parasite.
16 citations
References
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TL;DR: In this article, the authors developed a mathematic model to characterize the mechanical properties of single-walled carbon nanotubes (SWCNTs) by modeling the carbon-carbon (C-C) bonds between two adjacent atoms as Euler beams.
Abstract: This paper aims at developing a mathematic model to characterize the mechanical properties of single-walled carbon nanotubes (SWCNTs). The carbon-carbon (C-C) bonds between two adjacent atoms are modeled as Euler beams. According to the relationship of Tersoff-Brenner force theory and potential energy acting on C-C bonds, material constants of beam element are determined at the atomic scale. Based on the elastic deformation energy and mechanical equilibrium of a unit in graphite sheet, simply form ED equations of calculating Young's modulus of armchair and zigzag graphite sheets are derived. Following with the geometrical relationship of SWCNTs in cylindrical coordinates and the structure mechanics approach, Young's modulus and Poisson's ratio of armchair and zigzag SWCNTs are also investigated. The results show that the approach to research mechanical properties of SWCNTs is a concise and valid method. We consider that it will be useful technique to progress on this type of investigation.
119 citations
TL;DR: A brief overview of the current treatment and the active principles of established drugs is provided, and the mechanisms of drug resistance and natural products that are promising leads for the development of novel chemotherapeutics are focused on.
Abstract: Epidemics of fatal visceral leishmaniasis caused by the intracellular protozoan Leishmania are a severe public health problem in tropical and subtropical regions of the world. One major drawback in the treatment of leishmaniasis is the emergence of resistance to current chemotherapeutics. Leishmanicidals have to be administered in low doses since commonly used drugs exhibit severe side effects, and hence drug resistance can appear rapidly. Since, to date, vaccination approaches have failed to enter clinical trials, chemotherapy based on small molecules is temporarily the exclusive treatment strategy. There is an urgent need for adding novel drugs with improved features to the pool of current chemotherapeutics. Many compounds derived from natural sources have pharmacological activities and may, thus, be of potential utility in drug development and biomedical research. Natural products, primarily plant-derived substances of diverse structural classes, have been described in the literature showing anti-leishmanial properties. In this review we provide a brief overview of the current treatment and the active principles of established drugs. Furthermore, we focus on the mechanisms of drug resistance and natural products that are promising leads for the development of novel chemotherapeutics.
112 citations
"Andrographolide engineered gold nan..." refers background in this paper
...Bioactives of plant origin with leishmanicidal activity and lesser risk of resistance development [18] can be useful alternatives in the current context....
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TL;DR: In spite of antileishmanial activity of nanoparticles under UV, IR, and dark conditions, these nanoparticles had high cytotoxicity on macrophages, which must be considered in future studies.
110 citations
"Andrographolide engineered gold nan..." refers background in this paper
...Metal or metal oxide nanoparticle applications in leishmania are limited with metal ones having the edge as their oxidative capacity lead to more damage to the parasite membrane, enzyme and DNA [42] But presence of inherent cellular toxicity is the major cause of concern for clinical success of both metal and metal oxide nanoparticle....
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TL;DR: New quercetin conjugated gold nanoparticles (QAunp) were successfully evaluated for the first time against leishmanial macrophage infections.
104 citations
"Andrographolide engineered gold nan..." refers background in this paper
...Thus, unlike our previous report of quercetin stabilized nano-gold at low temperature conditions [22], AG induced reduction of Auþ3 to Au required assistance by initiators like temperature and Figure 1....
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...Drug resistant Leishmania donovani cells were developed as per earlier reports from our group [22]....
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...Our previous report with flavonoid engineered nano-gold showed high selectivity and significant efficacy in both wild and drugresistant leishmaniasis [22]....
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TL;DR: Mannosylated drug-loaded liposome-treated animals showed a normal blood picture and splenic tissue histoarchitecture when compared with those treated with free drug or regular liposomal drug, and a drug-vehicle formulation may be considered for clinical trials.
Abstract: Despite the rapid development in medicinal and pharmaceutical technology, the targeting of drugs to phagocytic cells in macrophage-related diseases still remains a major unsolved problem. By using the mannosyl-fucosyl receptors on macrophages, attempts were made to target antileishmanial drugs encapsulated in mannosylated or fucosylated liposomes to treat experimental leishmaniasis in the hamster model. Mannosylated liposomes were found to be more potent in delivering antileishmanial drugs to phagocytic cells. Liposomes loaded with an indigenous drug, andrographolide, a labdane diterpenoid isolated from Indian medicinal plant Andrographis paniculata, were prepared and tested against experimental leishmaniasis in a hamster model. Mannosylated liposomes loaded with the drug were found to be most potent in reducing the parasitic burden in the spleen as well as in reducing the hepatic and renal toxicity. In addition, mannosylated drug-loaded liposome-treated animals showed a normal blood picture and splenic t...
99 citations
"Andrographolide engineered gold nan..." refers background in this paper
...Andrographolide (AG), is a member of the terpenoid family with reported leishmanicidal effect both invitro and in-vivo [20]....
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